We have established a neurochemical basis for the use of purified (F-18)-labeled L-6-F-dopa as a presynaptic imaging ligand for brain dopaminergic neurons. A potential clinical use of this PET imaging ligand for brain dopamine in determining degrees of brain damage in parkinsonian patients was demonstrated in this study by using the MPTP-induced primate model of parkinsonism. Despite a high background activity due to contamination, we were able to image striatal dopaminergic neurons in living monkeys by using the Scanitronix PET scanner at the NIH Clinical Center. The striatal (F-18)-labeled dopaminergic activity was diminished in the monkeys that received a partially purified (F-18)-labeled 6-F- dopa and indicates a need to purify further this PET imaging ligand prior to the application of this 6-F-dopa/PET procedure in humans. By using animal models of parkinsonism, we have also evaluated a new SPECT imaging ligand for D2 dopamine receptors, (I-123)-labeled IBZM (3-iodobenzylamide derivative). It has been shown that IBZM specifically binds to D2 dopamine receptors in the brain and is displaceable by both agonists and antagonists of the D2 dopamine receptor. The in vivo imaging of the D2 dopamine receptors in the caudate nucleus, nucleus accumbens, olfactory tubercle and the kidney were obtained within thirty minutes following the administration of the radioactively labeled IBZM. A denervation induced decrease in dopaminergic fibers and increase in D2 dopamine receptors in the basal ganglia of experimental parkinsonian animals have been imaged by using these pre- and post-synaptic imaging ligands. Thus, this pre-clinical study has demonstrated potential clinical uses of these imaging ligands for studying in vivo the dopaminergic activities in patients with neuropsychiatric on Parkinson disorders.